Lysosomal storage diseases. Sphingolipidoses — gangliosidoses
- 作者: Gorbunova V.N.1, Buchinskaia N.V.1,2, Liazina L.V.2, Vechkasova A.O.2
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隶属关系:
- Saint Petersburg State Pediatric Medical University
- Saint Petersburg State Medical Diagnostic Center (Genetic Medical Center)
- 期: 卷 14, 编号 4 (2023)
- 页面: 93-111
- 栏目: Наследственные болезни обмена
- URL: https://journals.eco-vector.com/pediatr/article/view/623715
- DOI: https://doi.org/10.17816/PED14493-111
- ID: 623715
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详细
Epidemiology, clinical, biochemical and molecular genetic characteristics of gangliosidoses, genetically heterogeneous group of autosomal recessive diseases caused by hereditary deficiency of lysosomal glycohydrolases involved in the catabolism of GM1-, GM2- and GA2-gangliosides, are presented. Three clinical forms of GM1 gangliosidosis are caused by hereditary deficiency of lysosomal β-galactosidase, one of the activities of which is the release of galactose from carbohydrate complexes. As a result, GM1-ganglioside and, to a lesser extent, keratan sulfate accumulate in the lysosomes of neurons and other cells. Three genetically heterogeneous forms of GM2-gangliosidosis are associated with dysfunction of hexosaminidase activity. Tay–Sachs disease, or GM2 ganglioside variant B, is caused by mutations in the hexosaminidase alpha chain HEXA gene. Sandhoff’s disease is associated with mutations in the HEXB gene for the hexosaminidase beta chain. In this case, there is a deficiency of the A and B components of the enzyme — the null variant of GM2 gangliosidosis. In variant AB, or juvenile GM2 gangliosidosis, all hexosaminidase components are present, but the activating factor is defective due to mutations in the GM2A gene. All types of gangliosidosis are characterized by progressive retardation of psychomotor development and early death of patients, most often under the age of 3 years. The frequency of various types of gangliosidoses in different populations does not exceed 1 : 300,000. An exception is the ethic group of Ashkenazi Jews, in which the incidence of Tay–Sachs disease, reaches 1 : 3000, which makes total screening of heterozygotes and prenatal diagnosis of the disease in high-risk families economically justified. The article highlights the importance of experimental models for studying the molecular basis of pathogenesis and developing various therapeutic approaches, such as bone marrow transplantation, enzyme replacement therapy and substrate reducing therapy, gene therapy, and genome editing. Clinical examples of patients with gangliosidosis are given to improve the efficiency of diagnostics of these rare diseases by clinicians.
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作者简介
Viktoria Gorbunova
Saint Petersburg State Pediatric Medical University
编辑信件的主要联系方式.
Email: vngor@mail.ru
PhD, Dr. Sci. (Biol.), Professor, Department of General and Molecular Medical Genetics
俄罗斯联邦, Saint PetersburgNatalia Buchinskaia
Saint Petersburg State Pediatric Medical University; Saint Petersburg State Medical Diagnostic Center (Genetic Medical Center)
Email: nbuchinskaia@gmail.com
ORCID iD: 0000-0002-2335-3023
SPIN 代码: 4820-4246
MD, PhD pediatrician, geneticist, Consulting Department
俄罗斯联邦, Saint Petersburg; Saint PetersburgLidia Liazina
Saint Petersburg State Medical Diagnostic Center (Genetic Medical Center)
Email: mgccons@mail.ru
ORCID iD: 0000-0002-1252-1968
MD, PhD geneticist, Consulting Department
俄罗斯联邦, Saint PetersburgAnastasia Vechkasova
Saint Petersburg State Medical Diagnostic Center (Genetic Medical Center)
Email: vechkasova.nastia@mail.ru
ORCID iD: 0009-0004-8775-9630
General Practitioner, Resident Geneticist
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